The purpose of this project is to determine the molecular events involved in the biosynthesis and activation of eosinophil and neutrophil granule proteins. Studies in progress focus on A. granule protein folding, B. specific granule deficiency, and C. released granule proteins A. Protein folding. We have described the high affinity, reversible interaction of the prokaryotic molecular chaperone, groEL, with nascent chains of two eosinophil granule proteins. Using a panel of monoclonal antibodies, we have identified a novel protein present in early myeloid progenitors that shares at least one epitope with groEL. This protein is not present in mature peripheral blood cells. Further characterization of this protein is in progress. B. Specific granule deficiency. We have shown that the disorder known as neutrophil specific granule deficiency also includes the eosinophil lineage. We have shown that three of four eosinophil granule proteins are absent from peripheral blood cells from a patient with neutrophils specific granule deficiency. C. Released granule proteins. Using monoclonal antibodies that distinguish between storage and secreted form of an eosinophil granule protein, we have results suggesting that the released protein is deglycosylated relative to the storage form. The molecular events yielding this deglycosylation are under study.